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Find video protocols related to scientific articles indexed in Pubmed.
Plasma lipids and cerebral small vessel disease.
Neurology
PUBLISHED: 10-15-2014
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We examined the cross-sectional association between lipid fractions and 2 MRI markers of cerebral small vessel disease, white matter hyperintensity volume (WMHV) and lacunes, representing powerful predictors of stroke and dementia.
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Nutritional status in community-dwelling elderly in France in urban and rural areas.
PLoS ONE
PUBLISHED: 08-18-2014
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Malnutrition is a frequent condition in elderly people, especially in nursing homes and geriatric wards. Its frequency is less well known among elderly living at home. The objective of this study was to describe the nutritional status evaluated by the Mini Nutritional Assessment (MNA) of elderly community-dwellers living in rural and urban areas in France and to investigate its associated factors.
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Survival and early recourse to care for dementia: A population based study.
Alzheimers Dement
PUBLISHED: 08-14-2014
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A large proportion of dementia cases are still undiagnosed. Although early dementia care has been hypothesized to benefit both patients and families, evidence-based benefits are lacking. Thus, investigating the benefits for newly demented persons according to their recourse to care in the "real life" appears critical.
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Estrogen receptor polymorphisms and incident dementia: the prospective 3C study.
Alzheimers Dement
PUBLISHED: 08-12-2014
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Genetic variation in the estrogen receptor (ESR) may be associated with the incidence of Alzheimer's disease (AD), but this association could be modified by genetic and environmental factors.
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Quantifying and comparing dynamic predictive accuracy of joint models for longitudinal marker and time-to-event in presence of censoring and competing risks.
Biometrics
PUBLISHED: 06-01-2014
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Thanks to the growing interest in personalized medicine, joint modeling of longitudinal marker and time-to-event data has recently started to be used to derive dynamic individual risk predictions. Individual predictions are called dynamic because they are updated when information on the subject's health profile grows with time. We focus in this work on statistical methods for quantifying and comparing dynamic predictive accuracy of this kind of prognostic models, accounting for right censoring and possibly competing events. Dynamic area under the ROC curve (AUC) and Brier Score (BS) are used to quantify predictive accuracy. Nonparametric inverse probability of censoring weighting is used to estimate dynamic curves of AUC and BS as functions of the time at which predictions are made. Asymptotic results are established and both pointwise confidence intervals and simultaneous confidence bands are derived. Tests are also proposed to compare the dynamic prediction accuracy curves of two prognostic models. The finite sample behavior of the inference procedures is assessed via simulations. We apply the proposed methodology to compare various prediction models using repeated measures of two psychometric tests to predict dementia in the elderly, accounting for the competing risk of death. Models are estimated on the French Paquid cohort and predictive accuracies are evaluated and compared on the French Three-City cohort.
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Time may not fully attenuate solvent-associated cognitive deficits in highly exposed workers.
Neurology
PUBLISHED: 05-14-2014
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To test the effects of lifetime occupational solvent exposure, as measured by dose and timing, on performance on multiple cognitive tests among retired French utility workers.
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Gender-specific associations between lipids and cognitive decline in the elderly.
Eur Neuropsychopharmacol
PUBLISHED: 02-07-2014
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The aim of this study was to examine the associations between serum lipid levels and cognitive function in a community-based sample of non-demented subjects aged 65 years and over. Participants were 2737 men and 4118 women from a population-based cohort recruited from three French cities. Visual memory, verbal fluency, psychomotor speed, and executive abilities were evaluated at baseline, and after 2, 4, and 7 years of follow-up. Lipid levels were evaluated at baseline. Multiadjusted Cox models stratified by gender were adjusted for sociodemographic and lifestyle characteristics, mental and physical health, and genetic vulnerability to dyslipidemia (apolipoprotein E and A, and cholesteryl ester transfer protein) and taking into account baseline vascular pathologies. In men, a hypercholesterolemic pattern in late-life (high total cholesterol (T-C), low HDL-C, high LDL-C levels) was associated with a 25 to 50% increased risk of decline over 7 years in psychomotor speed, executive abilities, and verbal fluency. Specific associations with low T-C and low LDL-C levels were also observed which may depend on genetic vulnerability to dyslipidemia (related to apolipoprotein A5 and cholesteryl exchange transfer protein). In contrast, in women, a 30% higher rate of decline was found in psychomotor speed with high HDL-C levels and in executive abilities with low levels of LDL-C and triglycerides, in interaction with hormonal treatment. For men and women, vascular pathologies only slightly outweighed the risk related to lipids. This suggests a complex gender-specific pattern of cognitive decline involving genetic vulnerability in men and hormonal status in women.
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Normalized mini-mental state examination for assessing cognitive change in population-based brain aging studies.
Neuroepidemiology
PUBLISHED: 01-05-2014
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The Mini-Mental State Examination (MMSE) is widely used in population-based longitudinal studies to quantify cognitive change. However, its poor metrological properties, mainly ceiling/floor effects and varying sensitivity to change, have largely restricted its usefulness. We propose a normalizing transformation that corrects these properties, and makes possible the use of standard statistical methods to analyze change in MMSE scores.
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Plasma ?-amyloid 40 levels are positively associated with mortality risks in the elderly.
Alzheimers Dement
PUBLISHED: 01-02-2014
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We evaluated if plasma ?-amyloid (A?) levels were associated with mortality risks in a subsample of the French Three-City (3C) prospective cohort study.
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Gene-wide analysis detects two new susceptibility genes for Alzheimer's disease.
Valentina Escott-Price, Celine Bellenguez, Li-San Wang, Seung-Hoan Choi, Denise Harold, Lesley Jones, Peter Holmans, Amy Gerrish, Alexey Vedernikov, Alexander Richards, Anita L Destefano, Jean-Charles Lambert, Carla A Ibrahim-Verbaas, Adam C Naj, Rebecca Sims, Gyungah Jun, Joshua C Bis, Gary W Beecham, Benjamin Grenier-Boley, Giancarlo Russo, Tricia A Thornton-Wells, Nicola Denning, Albert V Smith, Vincent Chouraki, Charlene Thomas, M Arfan Ikram, Diana Zelenika, Badri N Vardarajan, Yoichiro Kamatani, Chiao-Feng Lin, Helena Schmidt, Brian Kunkle, Melanie L Dunstan, Maria Vronskaya, , Andrew D Johnson, Agustin Ruíz, Marie-Therese Bihoreau, Christiane Reitz, Florence Pasquier, Paul Hollingworth, Olivier Hanon, Annette L Fitzpatrick, Joseph D Buxbaum, Dominique Campion, Paul K Crane, Clinton Baldwin, Tim Becker, Vilmundur Gudnason, Carlos Cruchaga, David Craig, Najaf Amin, Claudine Berr, Oscar L Lopez, Philip L De Jager, Vincent Deramecourt, Janet A Johnston, Denis Evans, Simon Lovestone, Luc Letenneur, Isabel Hernández, David C Rubinsztein, Gudny Eiriksdottir, Kristel Sleegers, Alison M Goate, Nathalie Fiévet, Matthew J Huentelman, Michael Gill, Kristelle Brown, M Ilyas Kamboh, Lina Keller, Pascale Barberger-Gateau, Bernadette McGuinness, Eric B Larson, Amanda J Myers, Carole Dufouil, Stephen Todd, David Wallon, Seth Love, Ekaterina Rogaeva, John Gallacher, Peter St George-Hyslop, Jordi Clarimón, Alberto Lleó, Anthony Bayer, Debby W Tsuang, Lei Yu, Magda Tsolaki, Paola Bossù, Gianfranco Spalletta, Petra Proitsi, John Collinge, Sandro Sorbi, Florentino Sanchez Garcia, Nick C Fox, John Hardy, Maria Candida Deniz Naranjo, Paolo Bosco, Robert Clarke, Carol Brayne, Daniela Galimberti, Elio Scarpini, Ubaldo Bonuccelli, Michelangelo Mancuso, Gabriele Siciliano, Susanne Moebus, Patrizia Mecocci, Maria Del Zompo, Wolfgang Maier, Harald Hampel, Alberto Pilotto, Ana Frank-García, Francesco Panza, Vincenzo Solfrizzi, Paolo Caffarra, Benedetta Nacmias, William Perry, Manuel Mayhaus, Lars Lannfelt, Hakon Hakonarson, Sabrina Pichler, Minerva M Carrasquillo, Martin Ingelsson, Duane Beekly, Victoria Alvarez, Fanggeng Zou, Otto Valladares, Steven G Younkin, Eliecer Coto, Kara L Hamilton-Nelson, Wei Gu, Cristina Razquin, Pau Pastor, Ignacio Mateo, Michael J Owen, Kelley M Faber, Palmi V Jonsson, Onofre Combarros, Michael C O'Donovan, Laura B Cantwell, Hilkka Soininen, Deborah Blacker, Simon Mead, Thomas H Mosley, David A Bennett, Tamara B Harris, Laura Fratiglioni, Clive Holmes, Renée F A G de Bruijn, Peter Passmore, Thomas J Montine, Karolien Bettens, Jerome I Rotter, Alexis Brice, Kevin Morgan, Tatiana M Foroud, Walter A Kukull, Didier Hannequin, John F Powell, Michael A Nalls, Karen Ritchie, Kathryn L Lunetta, John S K Kauwe, Eric Boerwinkle, Matthias Riemenschneider, Mercè Boada, Mikko Hiltunen, Eden R Martin, Reinhold Schmidt, Dan Rujescu, Jean-Francois Dartigues, Richard Mayeux, Christophe Tzourio, Albert Hofman, Markus M Nöthen, Caroline Graff, Bruce M Psaty, Jonathan L Haines, Mark Lathrop, Margaret A Pericak-Vance, Lenore J Launer, Christine Van Broeckhoven, Lindsay A Farrer, Cornelia M van Duijn, Alfredo Ramírez, Sudha Seshadri, Gerard D Schellenberg, Philippe Amouyel, Julie Williams.
PLoS ONE
PUBLISHED: 01-01-2014
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Alzheimer's disease is a common debilitating dementia with known heritability, for which 20 late onset susceptibility loci have been identified, but more remain to be discovered. This study sought to identify new susceptibility genes, using an alternative gene-wide analytical approach which tests for patterns of association within genes, in the powerful genome-wide association dataset of the International Genomics of Alzheimer's Project Consortium, comprising over 7 m genotypes from 25,580 Alzheimer's cases and 48,466 controls.
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Hypnotics and mortality in an elderly general population: a 12-year prospective study.
BMC Med
PUBLISHED: 07-25-2013
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Hypnotics are widely used by the elderly, and their impact on mortality remains controversial. The inconsistent findings could be due to methodological limitations, notably the lack of control for underlying sleep symptoms or illness associated with hypnotic use, for example, insomnia symptoms and excessive daytime sleepiness, depression and anxiety. Our objective was to examine the association between the use of hypnotics and mortality risk in a large cohort of community-dwelling elderly, taking into account a wide range of potential competing risks including sociodemographic characteristics, lifestyle, and chronic disorders as well as underlying psychiatric disorders and sleep complaints.
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Metabolic syndrome and disability: findings from the prospective three-city study.
J. Gerontol. A Biol. Sci. Med. Sci.
PUBLISHED: 07-05-2013
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Metabolic syndrome (MetS) is a potentially reversible cause of disability in the elderly people. The published literature suggests that the MetS-disability association is likely to be complex, depending on co-existing risk factors and with possible variation for each of the specific MetS components. Further evidence is needed to understand the specific consequences of the MetS as a whole and as a function of its components.
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[Determinants of support for dementia patients in general practice: a qualitative approach based on an epidemiological cohort].
Geriatr Psychol Neuropsychiatr Vieil
PUBLISHED: 06-28-2013
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the analysis of access to diagnosis and care pathway for dementia patients shows that the disease is not considered as a priority for the general practitioner (GP). Different studies have point out under diagnosis of dementia.
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Relationship between diet and plasma long-chain n-3 PUFAs in older people: impact of apolipoprotein E genotype.
J. Lipid Res.
PUBLISHED: 06-25-2013
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The main risk factors for Alzheimers disease, age and the ?4 allele of the APOE gene (APOE4), might modify the metabolism of n-3 PUFAs and in turn, their impact on cognition. The aim of this study was to investigate the association between dietary fat and plasma concentrations of eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA) in elderly persons, taking the APOE4 genotype into account. The sample was composed of 1,135 participants from the Three-City study aged 65 years and over, of whom 19% were APOE4 carriers. Mean plasma proportions of EPA [1.01%, standard deviation (SD) 0.60] and DHA (2.41%, SD 0.81) did not differ according to APOE4. In multivariate models, plasma EPA increased with frequency of fish consumption (P < 0.0001), alcohol intake (P = 0.0006), and female gender (P = 0.02), and decreased with intensive consumption of n-6 oils (P = 0.02). The positive association between fish consumption and plasma DHA was highly significant whatever the APOE genotype (P < 0.0001) but stronger in APOE4 noncarriers than in carriers (P = 0.06 for interaction). Plasma DHA increased significantly with age (P = 0.009) in APOE4 noncarriers only. These findings suggest that dietary habits, gender, and APOE4 genotype should be considered when designing interventions to increase n-3 PUFA blood levels in older people.
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Prospective analysis of the association between estrogen receptor gene variants and the risk of cognitive decline in elderly women.
Eur Neuropsychopharmacol
PUBLISHED: 05-20-2013
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A plethora of data suggests a role for estrogen in cognitive function and genetic variants in the estrogen receptors ESR1 and ESR2 have been implicated in a range of hormone-sensitive diseases. It remains unknown however, whether ESR polymorphisms are associated with the risk of decline in specific domains of cognitive function. Data came from 3799 non-demented, community-dwelling elderly women recruited in France to the 3C Study. A short cognitive test battery was administered at baseline and 2, 4 and 7 years follow-up to assess global function, verbal fluency, visual memory, psychomotor speed and executive function. Detailed socio-demographic, behavioral, physical and mental health information was also gathered and genotyping of five common ESR1 and ESR2 polymorphisms was also performed. In multivariable-adjusted Cox analysis, ESR1 rs2234693 and rs9340799 were not significantly associated with the risk of decline on any of the cognitive tasks. However, significant associations with ESR2 polymorphisms were identified. The A allele of rs1256049 was associated with an increased risk of substantial decline in visual memory (HR:1.64, 95% CI: 1.23-2.18, p=0.0007), psychomotor speed (HR:1.43, 95% CI: 1.12-1.83, p=0.004), and on the incidence of Mild Cognitive Impairment (HR:1.31, 95% CI: 1.05-1.64, p=0.02). There was also a weaker association between the A allele of rs4986938 and a decreased risk of decline in psychomotor speed. Our large multicentre prospective study provides preliminary evidence that ESR2 genetic variants may be associated with specific cognitive domains and suggests that further examination of the role of this gene in cognitive function is warranted.
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Subjective cognitive complaints and mortality: Does the type of complaint matter?
J Psychiatr Res
PUBLISHED: 05-18-2013
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Middle-aged subjects report subjective cognitive complaints (SSCs) but whether these are meaningfully related to health remains unknown. We examined the association between SCCs, both amnestic and non-amnestic, and mortality in a middle-aged population after taking into account the role of depression. 15,510 participants (26.2% women), mean age 57.9 years in 2002, from the French GAZEL study provided data on 3 measures of SCCs: memory complaints, cognitive symptoms (forgetfulness, difficulties in recalling memories, retaining new information, mental calculation, in language, and orientation) and whether they sought medical advice for SCCs. All-cause mortality was assessed between 2002 and 2012. Over the follow-up 56.3% participants reported memory problems, 62.6% cognitive complaints, 22.3% sought medical advice and 651 died. All SCCs were strongly associated (odds ratio 2.08-6.35) with depression which was itself associated with greater mortality (HR = 1.77, 95% CI: 1.50, 2.09). In analyses adjusted for age, sex, education, marital status and depression difficulty in mental calculation (HR = 1.30, 95% CI: 1.08, 1.60) and seeking medical advice for cognitive symptoms (HR = 1.41, 95% CI: 1.18, 1.68) were significantly associated with mortality, while memory complaints did not carry increased risk (HR = 0.93, 95% CI: 0.79, 1.09). All SCCS were strongly associated with depression but not all carried excess risk of mortality.
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Education Modulates the Impact of White Matter Lesions on the Risk of Mild Cognitive Impairment and Dementia.
Am J Geriatr Psychiatry
PUBLISHED: 01-29-2013
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Conflicting results have been reported regarding the association between white matter lesions (WML) and cognitive impairment. We hypothesized that education, a marker of cognitive reserve (CR), could modulate the effects of WML on the risk of mild cognitive impairment (MCI) or dementia.
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Spatial distribution of cerebral white matter lesions predicts progression to mild cognitive impairment and dementia.
PLoS ONE
PUBLISHED: 01-17-2013
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White matter lesions (WML) increase the risk of dementia. The relevance of WML location is less clear. We sought to determine whether a particular WML profile, based on the density and location of lesions, could be associated with an increased risk of mild cognitive impairment (MCI) or dementia over the following 7 years.
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A prospective study of the bi-directional association between vision loss and depression in the elderly.
J Affect Disord
PUBLISHED: 01-09-2013
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Increasing visual impairment (VI) with age has been associated with mental health problems but the question of temporal direction and reverse causality has not been addressed previously. Our objective was to prospectively examine the bi-directional association of VI and visual function (VF) loss with depressive symptoms in the elderly.
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Gender Differences in the Association between Socioeconomic Status and Subclinical Atherosclerosis.
PLoS ONE
PUBLISHED: 01-01-2013
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This study explored the pattern of associations between socioeconomic status (SES) and atherosclerosis progression (as indicated by carotid intima media thickness, CIMT) across gender.
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Abdominal obesity and late-onset asthma: cross-sectional and longitudinal results: the 3C study.
Obesity (Silver Spring)
PUBLISHED: 10-20-2011
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Whereas global obesity assessed by BMI has been related to asthma risk, little is known as to the potential implication of abdominal adiposity in this relationship. In the elderly, in whom asthma remains poorly studied, abdominal adiposity tends to increase at the expense of muscle mass. The purpose of this study was to investigate the association between abdominal adiposity, assessed by waist circumference (WC), and prevalence and incidence of asthma in a large elderly cohort. Cross-sectional analysis was based on 7,643 participants aged ?65 years including 592 (7.7%) with lifetime physician-diagnosed asthma. Longitudinal analysis involved 6,267 baseline nonasthmatics followed-up for a period of 4 years, 67 of whom exhibited incident asthma. Baseline WC was categorized according to sex-specific criteria (men/women): <94/80 cm (reference), [94-102[/[80-88[ (abdominal overweight), and ?102/88 (abdominal obesity). Logistic and Cox regression models estimated asthma risk associated with WC after adjustment for age, sex, educational level, smoking status, BMI, physical ability, dyspnea, chronic bronchitis symptoms and history of cardiovascular disease. At baseline, asthma risk increased with increasing WC independently of BMI and other confounders (adjusted odds ratio (ORa), 95% confidence interval (CI): 1.30, 1.02-1.65 and ORa: 1.76, 1.31-2.36 for abdominal overweight and obesity, respectively). Asthma incidence was related to WC (hazard ratio (HRa), 95% CI: 2.69, 1.21-5.98 and HRa: 3.84, 1.55-9.49, for abdominal overweight and obesity, respectively). Estimates were similar in both sexes. In the elderly, abdominal adiposity was independently associated with increased prevalence and incidence of asthma. Studies aiming to understand the mechanisms involved in the adiposity-asthma link are needed.
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Epidemiology and prognostic significance of chronic kidney disease in the elderly--the Three-City prospective cohort study.
Nephrol. Dial. Transplant.
PUBLISHED: 06-15-2011
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Little is known about normal kidney function level and the prognostic significance of low estimated glomerular filtration rate (eGFR) in the elderly.
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Alternative Healthy Eating Index and mortality over 18 y of follow-up: results from the Whitehall II cohort.
Am. J. Clin. Nutr.
PUBLISHED: 05-25-2011
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Indexes of diet quality have been shown to be associated with decreased risk of mortality in several countries. It remains unclear if the Alternative Healthy Eating Index (AHEI), designed to provide dietary guidelines to combat major chronic diseases, is related to mortality risk.
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Late life depression and incident activity limitations: influence of gender and symptom severity.
J Affect Disord
PUBLISHED: 03-10-2011
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Mental disorders, especially depression, are one of the principal causes of disablement. Previous research has been limited partly due to the failure to take into account sub-syndromal states and the very large number of candidate mediating and confounding factors.
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Common variants at ABCA7, MS4A6A/MS4A4E, EPHA1, CD33 and CD2AP are associated with Alzheimers disease.
Paul Hollingworth, Denise Harold, Rebecca Sims, Amy Gerrish, Jean-Charles Lambert, Minerva M Carrasquillo, Richard Abraham, Marian L Hamshere, Jaspreet Singh Pahwa, Valentina Moskvina, Kimberley Dowzell, Nicola Jones, Alexandra Stretton, Charlene Thomas, Alex Richards, Dobril Ivanov, Caroline Widdowson, Jade Chapman, Simon Lovestone, John Powell, Petroula Proitsi, Michelle K Lupton, Carol Brayne, David C Rubinsztein, Michael Gill, Brian Lawlor, Aoibhinn Lynch, Kristelle S Brown, Peter A Passmore, David Craig, Bernadette McGuinness, Stephen Todd, Clive Holmes, David Mann, A David Smith, Helen Beaumont, Donald Warden, Gordon Wilcock, Seth Love, Patrick G Kehoe, Nigel M Hooper, Emma R L C Vardy, John Hardy, Simon Mead, Nick C Fox, Martin Rossor, John Collinge, Wolfgang Maier, Frank Jessen, Eckart Rüther, Britta Schürmann, Reiner Heun, Heike Kölsch, Hendrik van den Bussche, Isabella Heuser, Johannes Kornhuber, Jens Wiltfang, Martin Dichgans, Lutz Frölich, Harald Hampel, John Gallacher, Michael Hüll, Dan Rujescu, Ina Giegling, Alison M Goate, John S K Kauwe, Carlos Cruchaga, Petra Nowotny, John C Morris, Kevin Mayo, Kristel Sleegers, Karolien Bettens, Sebastiaan Engelborghs, Peter P De Deyn, Christine Van Broeckhoven, Gill Livingston, Nicholas J Bass, Hugh Gurling, Andrew McQuillin, Rhian Gwilliam, Panagiotis Deloukas, Ammar Al-Chalabi, Christopher E Shaw, Magda Tsolaki, Andrew B Singleton, Rita Guerreiro, Thomas W Mühleisen, Markus M Nöthen, Susanne Moebus, Karl-Heinz Jöckel, Norman Klopp, H-Erich Wichmann, V Shane Pankratz, Sigrid B Sando, Jan O Aasly, Maria Barcikowska, Zbigniew K Wszolek, Dennis W Dickson, Neill R Graff-Radford, Ronald C Petersen, , Cornelia M van Duijn, Monique M B Breteler, M Arfan Ikram, Anita L Destefano, Annette L Fitzpatrick, Oscar Lopez, Lenore J Launer, Sudha Seshadri, Claudine Berr, Dominique Campion, Jacques Epelbaum, Jean-Francois Dartigues, Christophe Tzourio, Annick Alpérovitch, Mark Lathrop, Thomas M Feulner, Patricia Friedrich, Caterina Riehle, Michael Krawczak, Stefan Schreiber, Manuel Mayhaus, S Nicolhaus, Stefan Wagenpfeil, Stacy Steinberg, Hreinn Stefansson, Kari Stefansson, Jón Snaedal, Sigurbjorn Bjornsson, Palmi V Jonsson, Vincent Chouraki, Benjamin Genier-Boley, Mikko Hiltunen, Hilkka Soininen, Onofre Combarros, Diana Zelenika, Marc Delepine, María J Bullido, Florence Pasquier, Ignacio Mateo, Ana Frank-García, Elisa Porcellini, Olivier Hanon, Eliecer Coto, Victoria Alvarez, Paolo Bosco, Gabriele Siciliano, Michelangelo Mancuso, Francesco Panza, Vincenzo Solfrizzi, Benedetta Nacmias, Sandro Sorbi, Paola Bossù, Paola Piccardi, Beatrice Arosio, Giorgio Annoni, Davide Seripa, Alberto Pilotto, Elio Scarpini, Daniela Galimberti, Alexis Brice, Didier Hannequin, Federico Licastro, Lesley Jones, Peter A Holmans, Thorlakur Jonsson, Matthias Riemenschneider, Kevin Morgan, Steven G Younkin, Michael J Owen, Michael O'Donovan, Philippe Amouyel, Julie Williams.
Nat. Genet.
PUBLISHED: 03-10-2011
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We sought to identify new susceptibility loci for Alzheimers disease through a staged association study (GERAD+) and by testing suggestive loci reported by the Alzheimers Disease Genetic Consortium (ADGC) in a companion paper. We undertook a combined analysis of four genome-wide association datasets (stage 1) and identified ten newly associated variants with P ? 1 × 10(-5). We tested these variants for association in an independent sample (stage 2). Three SNPs at two loci replicated and showed evidence for association in a further sample (stage 3). Meta-analyses of all data provided compelling evidence that ABCA7 (rs3764650, meta P = 4.5 × 10(-17); including ADGC data, meta P = 5.0 × 10(-21)) and the MS4A gene cluster (rs610932, meta P = 1.8 × 10(-14); including ADGC data, meta P = 1.2 × 10(-16)) are new Alzheimers disease susceptibility loci. We also found independent evidence for association for three loci reported by the ADGC, which, when combined, showed genome-wide significance: CD2AP (GERAD+, P = 8.0 × 10(-4); including ADGC data, meta P = 8.6 × 10(-9)), CD33 (GERAD+, P = 2.2 × 10(-4); including ADGC data, meta P = 1.6 × 10(-9)) and EPHA1 (GERAD+, P = 3.4 × 10(-4); including ADGC data, meta P = 6.0 × 10(-10)).
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Steroid and nonsteroidal anti-inflammatory drugs, cognitive decline, and dementia.
Neurobiol. Aging
PUBLISHED: 03-09-2011
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The aim of this study was to evaluate the effects of anti-inflammatory intake on cognitive function in 7234 community-dwelling elderly persons. Cognitive performance, clinical diagnosis of dementia, and anti-inflammatory use were evaluated at baseline, and 2, 4, and 7 years later. Multivariate logistic regression analyses were adjusted for sociodemographic, behavioral, physical, mental health variables, and genetic vulnerability (apolipoprotein E ?4). Elderly women taking inhaled corticosteroids were at increased risk for cognitive decline over 7 years in executive functioning (odds ratio, 1.76; 95% confidence interval, 1.14-2.71; p = 0.04); the effect being increased after continuous use (odds ratio, 3.15; 95% confidence interval, 1.29-7.68; p = 0.01) and not found after discontinuation of treatment. In men, no significant associations were observed. Corticosteroid use was not significantly associated with an increase risk of incident dementia over 7 years. Nonsteroidal anti-inflammatory drug use was not significantly associated with either dementia incidence or cognitive decline in both sexes. The association may be related to hypothalamic-pituitary-adrenal corticotropic axis dysfunctioning rather than a direct anti-inflammatory mechanism. Long-term use of inhaled corticosteroids may constitute a form of reversible cognitive disorder in elderly women. Physicians should check this possibility before assuming neurodegenerative changes.
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Metabolic syndrome and onset of depressive symptoms in the elderly: findings from the three-city study.
Diabetes Care
PUBLISHED: 02-23-2011
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Given the increasing prevalence of both metabolic syndrome (MetS) and depressive symptoms during old age, we aimed to examine prospectively the association between MetS and the onset of depressive symptoms according to different age-groups in a large, general elderly population.
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Inappropriate drug use and mortality in community-dwelling elderly with impaired kidney function--the Three-City population-based study.
Nephrol. Dial. Transplant.
PUBLISHED: 02-03-2011
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Glomerular filtration rate (GFR) decline with age increases the risk of inappropriate dosing of drugs. We investigated the determinants and the mortality associated with the use of drugs that are contraindicated or require dose adjustment according to kidney function among the community-dwelling elderly.
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Association of plasma Aß peptides with blood pressure in the elderly.
PLoS ONE
PUBLISHED: 01-05-2011
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Aß peptides are often considered as catabolic by-products of the amyloid ß protein precursor (APP), with unknown physiological functions. However, several biological properties have been tentatively attributed to these peptides, including a role in vasomotion. We assess whether plasma Aß peptide levels might be associated with systolic and diastolic blood pressure values (SBP and DBP, respectively).
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Retrospective identification and characterization of mild cognitive impairment from a prospective population cohort.
Am J Geriatr Psychiatry
PUBLISHED: 09-29-2010
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Mild cognitive impairment (MCI) case-finding criteria have low specificity in general population studies. This study retrospectively identifies cases of MCI and determines baseline criteria giving the highest discriminability. The ability of these criteria to increase current case detection specificity is estimated.
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High alcohol consumption in middle-aged adults is associated with poorer cognitive performance only in the low socio-economic group. Results from the GAZEL cohort study.
Addiction
PUBLISHED: 09-15-2010
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To examine the association of alcohol consumption over 10 years with cognitive performance in different socio-economic groups.
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Metabolic syndrome, its components, and mortality in the elderly.
J. Clin. Endocrinol. Metab.
PUBLISHED: 09-01-2010
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The metabolic syndrome (MetS) has been shown to predict mortality in the middle-aged, but less is known on the impact of MetS and its components on mortality risk in the elderly. Our objectives were 1) to examine the association of MetS with the risk of all-cause and cause-specific mortality in a French elderly community-dweller cohort and 2) to determine the main components driving these associations.
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Plasma selenium and risk of dysglycemia in an elderly French population: results from the prospective Epidemiology of Vascular Ageing Study.
Nutr Metab (Lond)
PUBLISHED: 03-18-2010
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A preventive role of selenium on the risk of diabetes has been reported and ascribed to the "insulin-like" activity of selenium and the antioxidant properties of the selenoenzymes. By contrast, data from cross-sectional studies and clinical trials have suggested an adverse effect of high selenium status and selenium supplementation on type-2 diabetes risk. Given these controversial results, we investigated prospectively the relationship between baseline plasma selenium concentration and occurrence of dysglycemia (impaired fasting glucose or type 2 diabetes) in an elderly French cohort.
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Validation study of a French version of the modified telephone interview for cognitive status (F-TICS-m) in elderly women.
Int J Geriatr Psychiatry
PUBLISHED: 01-08-2010
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To evaluate the performance of a French version of the modified Telephone Interview for Cognitive Status (F-TICS-m) in identifying cognitive decline among elderly women.
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Olive oil and cognition: results from the three-city study.
Dement Geriatr Cogn Disord
PUBLISHED: 09-02-2009
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Olive oil is a major component of the Mediterranean diet suggested to be beneficial to counteract Alzheimers disease. Aim of the Study: Our objective was to examine the association between olive oil use, cognitive deficit and cognitive decline in a large elderly population.
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[Epidemiology of Alzheimers disease: methodological approaches and new perspectives].
Psychol Neuropsychiatr Vieil
PUBLISHED: 07-21-2009
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Over the last 20 years, a number of epidemiological studies on Alzheimers disease (AD) have been conducted on large cohorts providing databases for studying the disease frequency, and leading to a more global overview of AD risk factors. However, precise identification of factors which potentiate or delay the pathological process of the disease is still incomplete. One of the major problems comes from difficulties for defining the cases and obtaining good clinical diagnoses in population-based studies. Moreover, it is difficult to determine the chronology of exposure-disease relationships whatever the factors studied: vascular factors, life habits (dietary habits, physical, social or intellectual activities...). Which life-course period is important for proposing interventions to modify these factors remains a central question. The longer follow-up of large cohorts and a better knowledge of potential risk factors constitute a research priority if we want to prevent efficiently AD in the near future.
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Total plasma carotenoids and mortality in the elderly: results of the Epidemiology of Vascular Ageing (EVA) study.
Br. J. Nutr.
PUBLISHED: 06-02-2009
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Carotenoids are pigments found in fruits and vegetables. While high intakes of fruits and vegetables have been found to be associated with lower mortality, our objective is to investigate if total plasma carotenoids, via their antioxidant properties, are associated with mortality risk in a free-living elderly population. The Epidemiology of Vascular Ageing (EVA) study (n 1389; 59-71 years) is a 9-year longitudinal study with six waves of follow-up. The association between baseline total plasma carotenoids and mortality was determined by Cox proportional hazards regression analyses. Low total plasma carotenoid level was significantly associated with all-cause mortality in men but not in women. After controlling for potential confounding factors, mortality risk increased significantly in men (P = 0.03) with plasma carotenoids in the lowest quintile compared with men with plasma carotenoids in the highest (relative risk 2.94 (95% CI 1.21, 7.17)). A significant association between mortality by cancer and low plasma carotenoid level variable was also found in men (unit = 1 micromol/l; relative risk 1.72 (95% CI 1.02, 2.86); P = 0.01). Associations between total plasma carotenoids and mortality risk remained statistically significant after taking into account: (1) plasma Se level, which previously was found associated with mortality in this population and (2) thiobarbituric acid-reactive substances level considered as an indicator of oxidative stress. By showing, prospectively, in a general healthy elderly population, that total plasma carotenoid levels were independently associated with mortality risk in men, the present study suggests that total plasma carotenoid levels could be a health indicator in elderly populations.
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Genome-wide association study identifies variants at CLU and CR1 associated with Alzheimers disease.
Nat. Genet.
PUBLISHED: 05-12-2009
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The gene encoding apolipoprotein E (APOE) on chromosome 19 is the only confirmed susceptibility locus for late-onset Alzheimers disease. To identify other risk loci, we conducted a large genome-wide association study of 2,032 individuals from France with Alzheimers disease (cases) and 5,328 controls. Markers outside APOE with suggestive evidence of association (P < 10(-5)) were examined in collections from Belgium, Finland, Italy and Spain totaling 3,978 Alzheimers disease cases and 3,297 controls. Two loci gave replicated evidence of association: one within CLU (also called APOJ), encoding clusterin or apolipoprotein J, on chromosome 8 (rs11136000, OR = 0.86, 95% CI 0.81-0.90, P = 7.5 x 10(-9) for combined data) and the other within CR1, encoding the complement component (3b/4b) receptor 1, on chromosome 1 (rs6656401, OR = 1.21, 95% CI 1.14-1.29, P = 3.7 x 10(-9) for combined data). Previous biological studies support roles of CLU and CR1 in the clearance of beta amyloid (Abeta) peptide, the principal constituent of amyloid plaques, which are one of the major brain lesions of individuals with Alzheimers disease.
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Performance of a short dietary questionnaire to assess nutrient intake using regression-based weights.
Public Health Nutr
PUBLISHED: 05-09-2009
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To evaluate the performance of a short dietary questionnaire, using weights to estimate nutrient intake.
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Fibrates but not statins increase plasma selenium in dyslipidemic aged patients--the EVA study.
J Trace Elem Med Biol
PUBLISHED: 02-11-2009
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This secondary analysis of "Etude du Vieillissement Artériel" (EVA) study reports the effect of fibrates and statins on plasma selenium concentration and its 9-year change in free-living dyslipidemic elderly. Dyslipidemic patients were categorized in three sub-groups according to final low-density lipoprotein (LDL)-cholesterol level or hypolipidemic treatment: non-treated dyslipidemic (LDL-cholesterol >4.41 mmol/L, n=84); dyslipidemics who were treated exclusively by fibrates (n=47) or by statins (n=25) whatever their serum LDL-cholesterol concentration. The influence of lipid-lowering treatments on plasma selenium concentrations and its 9-year change was evaluated by analysis of variance (ANOVA) and multivariate linear regression models taking into account cardiovascular risk and changes in lipid-profile parameters. Multivariate linear regression indicated that the plasma selenium decline was associated with the longitudinal variation in LDL (beta=-0.039+/-0.019, p=0.04) and high-density lipoprotein (HDL)-cholesterol concentrations (beta=0.187+/-0.059, p=0.002) but not with triglycerides (beta=-0.018+/-0.031, p=0.57). During the 9-year follow-up, similar plasma selenium declines were observed in all the sub-groups (p=0.33) despite plasma selenium levels being higher in fibrate users and lower in statin users (p=0.0004). The mechanisms underlying these data are not yet totally understood, but considering the risk of selenium deficiency in the elderly and its relationship with poor health status further clinical trial is needed to verify the proposed hypotheses.
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Long-term association of food and nutrient intakes with cognitive and functional decline: a 13-year follow-up study of elderly French women.
Br. J. Nutr.
PUBLISHED: 02-10-2009
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The objective of the present study was to determine the potential long-term impact of dietary habits on age-related decline among 4809 elderly women (born between 1925 and 1930) in the Etude Epidémiologique de Femmes de la Mutuelle Générale de lEducation Nationale (E3N) study, a French epidemiological cohort. In 1993, an extensive diet history self-administered questionnaire was sent to all participants, and in 2006 another questionnaire on instrumental activities of daily living (IADL) and recent cognitive change was sent to a close relative or friend of each woman. Logistic models adjusted for socio-demographic, lifestyle and health factors were performed to evaluate associations between habitual dietary intakes and two outcomes of interest based on the informant response: recent cognitive decline and IADL impairment. Recent cognitive decline was associated with lower intakes of poultry, fish, and animal fats, as well as higher intakes of dairy desserts and ice-cream. IADL impairment was associated with a lower intake of vegetables. The odds of recent cognitive decline increased significantly with decreasing intake of soluble dietary fibre and n-3 fatty acids but with increasing intake of retinol. The odds of IADL impairment increased significantly with decreasing intakes of vitamins B2, B6 and B12. These results are consistent with a possible long-term neuroprotective effect of dietary fibre, n-3 polyunsaturated fats and B-group vitamins, and support dietary intervention to prevent cognitive decline.
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Metabolic syndrome and risk for incident Alzheimers disease or vascular dementia: the Three-City Study.
Diabetes Care
PUBLISHED: 02-04-2009
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Associations between metabolic syndrome and its individual components with risk of incident dementia and its different subtypes are inconsistent.
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[Activities in retired people and the risk of dementia].
C. R. Biol.
PUBLISHED: 01-30-2009
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It is necessary to develop the prevention of Alzheimers disease, because of the increase in the number of cases and unavailability of a curative treatment. From the data of the cohort PAQUID, we studied the risk of dementia according to leisure activities and the age of cessation of professional activity. The practice of a sport and reading decreases by 25% the risk of dementia during 15 years. The age of cessation of professional activity is not associated with the risk of dementia. An active life seems to be a possible way to prevent dementia.
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Excessive sleepiness is predictive of cognitive decline in the elderly.
Sleep
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To examine the association of sleep complaints reported at baseline (insomnia complaints and excessive daytime sleepiness (EDS)) and medication, with cognitive decline in community-dwelling elderly.
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Mediterranean diet and cognitive decline in women with cardiovascular disease or risk factors.
J Acad Nutr Diet
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Cardiovascular disease and vascular risk factors increase rates of cognitive impairment, but very little is known regarding prevention in this high-risk group. The heart-healthy Mediterranean-type dietary pattern may beneficially influence both vascular and cognitive outcomes.
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Chronic use of benzodiazepines and latent cognitive decline in the elderly: results from the Three-city study.
Eur Neuropsychopharmacol
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We aimed to examine whether long-term use of benzodiazepines is associated with an accelerated decline of cognitive performances by using a statistical model specifically adapted to multivariate longitudinal bounded quantitative outcomes. The data came from the "Three-city" study, a French population based study. All the subjects were 65 years old or older at inclusion and had been followed-up for 7 years. The use of benzodiazepines and cognitive functioning were assessed at each examination phase (baseline, 2, 4 and 7 years). Cognitive decline was analyzed using a nonlinear multivariate mixed model with a latent process. This model makes it possible to assess change over time of the latent cognitive process underlying several neuropsychological tests: Mini Mental Status Examination, Isaacs Set test, Benton Visual Retention Test, and Trail Making Test (A and B), and to describe and account for their metrological properties. Analyses were adjusted for age, center, gender, education, socio-professional status, depression, insomnia, high blood pressure, hypercholesterolemia, alcohol, tobacco consumption and physical activity. Nine hundred and sixty nine subjects who reported taking benzodiazepines for 2, 4 or 7 consecutive years were compared to 4226 subjects who were non-benzodiazepine users. Chronic use of benzodiazepine was significantly associated with a lower latent cognitive level (?=-1.79 SE=0.25 p=<0.001), but no association was found between chronic use and an acceleration of cognitive decline, neither on the latent cognitive process (? × time=0.010 SE=0.04 p=0.81), nor on specific neuropsychological tests. Our results suggest that chronic benzodiazepine use is associated with poorer cognitive performance but not with accelerated cognitive decline with age.
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Anxiety symptoms and disorder predict activity limitations in the elderly.
J Affect Disord
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In the elderly, little attention has been paid to anxiety both on a symptom dimension and as a disorder, as an independent risk factor for the incidence of activity limitations.
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[How to define old age: successful aging and/or longevity].
Med Sci (Paris)
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In half a century, the number of nonagenarians and/or centenarians has dramatically increased, particularly due to the increase in life expectancy at old age. However, successful aging is more important than longevity. All along their life, people can act to preserve their health, their physical and mental abilities as well as their autonomy. This requires a healthy diet, having physical and intellectual appropriate activities and a right use of medical care. Finally, maintaining a social role and a raison dêtre in old age are also major factors in successful aging.
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Single polymorphism nucleotide rs1333049 on chromosome 9p21 is associated with carotid plaques but not with common carotid intima-media thickness in older adults. A combined analysis of the Three-City and the EVA studies.
Atherosclerosis
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To address the relationship of rs1333049, the 9p21 variant showing the strongest association with coronary heart disease (CHD), with carotid plaques and plaque-free common carotid artery intima-media thickness (CCA-IMT) in older adults from 2 French population-based cohorts.
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Selenium and cognitive impairment: a brief-review based on results from the EVA study.
Biofactors
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Preventing cognitive impairment and dementia in the elderly is a major public health challenge for our century and all hypotheses should be explored. Selenium (Se) is one of the factors that may affect the risk of cognitive decline. Its importance in the health and aging process has been documented. Because of the potential of selenoproteins to protect against oxidative stress, Se raises significant expectations for the prevention of chronic diseases including cancer, cardiovascular disease, and type 2 diabetes conditions commonly associated with oxidative stress. Thus, the relationships between Se and cognitive impairment or dementia can be examined through vascular risk factors for dementia, with particular interest in diabetes and dyslipidemia. In addition, in cases of Se deficiency, the brain is the organ that remains Se replete the longest suggesting that Se plays an important role in brain functions. This article presents results obtained in the frame of a longitudinal study on Se and cognitive impairment. They are consistent with the hypothesis that low Se status is a risk factor for cognitive decline even after taking into account vascular risk factors. The concomitant evolution between plasma Se decrease over a 9-year period and cognitive decline suggested that optimal Se status is potentially important to maintain neuropsychological functions in aging people. However, as our understanding of Se biology is incomplete, epidemiological studies are needed to define the groups of population that could benefit from Se supplementation.
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Timing of onset of cognitive decline: results from Whitehall II prospective cohort study.
BMJ
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To estimate 10 year decline in cognitive function from longitudinal data in a middle aged cohort and to examine whether age cohorts can be compared with cross sectional data to infer the effect of age on cognitive decline.
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